INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Wenyao Yang,Juanzhu Han,Liping Zhang,Yunsong Sun,Yuchen Zhu,Yiyu Liu,Jingyu Chen,Xiaoyao Liao,Hui Liao,Weizhuo Xu,Yongbo Song
Skeletal muscle inflammation associated with sepsis has been identified as a critical pathological process contributing to metabolic dysfunction and poor clinical outcomes. Voltage-gated sodium channels (VGSCs) have been implicated in immune modulation; however, their specific roles in skeletal muscle inflammation remain poorly understood. In this study, the VGSC subtype Nav1.5 was investigated as a potential regulator of inflammation, and the therapeutic efficacy of a novel recombinant scorpion peptide, DKK678, was evaluated. An in vitro model using lipopolysaccharide (LPS)-stimulated C2C12 cells and an in vivo cecal ligation and puncture (CLP) model in septic mice were established. In both models, Nav1.5 expression was significantly upregulated in response to inflammatory stimuli, while Nav1.4 expression remained unchanged. The nuclear factor kappa B (NF-κB) signaling pathway was found to be activated, contributing to increased expression of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), adhesion molecules (VCAM-1), and gap junction proteins (Cx43). Suppression of VGSC activity using lidocaine resulted in the inhibition of NF-κB phosphorylation and downregulation of inflammatory markers, while the expression of interleukin-10 (IL-10) and interleukin-4 (IL-4) were restored. Tetrodotoxin (TTX) treatment did not replicate these effects, suggesting Nav1.5-specific involvement. DKK678 was developed through bioinformatic design and molecular docking simulations, which predicted a stronger binding affinity and structural stability with Nav1.5 compared to Nav1.4. These predictions were validated through functional experiments. In vitro, DKK678 treatment dose-dependently inhibited LPS-induced NF-κB pathway activation and reversed abnormal expression of VCAM-1 and Cx43. In vivo, DKK678 significantly ameliorated CLP-induced skeletal muscle damage, suppressed inflammatory cytokine production, and improved tissue histopathology. Furthermore, the structural integrity of immune organs such as the thymus and spleen was preserved in DKK678-treated septic mice, with partial restoration of lymphocyte populations and organ indices. Notably, Nav1.5 expression was downregulated by DKK678, while Nav1.4 expression remained unaffected. These results demonstrate that Nav1.5 serves as a critical inflammatory modulator in skeletal muscle and immune tissues. Its upregulation was shown to drive NF-κB pathway activation and inflammatory cytokine production. By targeting Nav1.5, DKK678 was able to exert dual protective effects on both skeletal muscle and immune organs under septic conditions. The therapeutic potential of DKK678 was found to be comparable to that of dexamethasone (DEX) at high doses, without altering Nav1.4 expression. In conclusion, the present study provides new mechanistic insight into the role of Nav1.5 in skeletal muscle inflammation and identifies DKK678 as a promising peptide therapeutic that targets Nav1.5 to suppress NF-κB-mediated inflammatory injury. These findings suggest that Nav1.5 inhibition represents a viable strategy for the treatment of sepsis-associated myositis and related inflammatory disorders.
研究领域:
免疫学
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药理学
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分子生物学
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病理学
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-18
·
IF 12.6
Wang Yingqian,Ma Zeqiang,Jiang Lehua,Bojan Nataraj,Sha Yiwen,Huang Boyu,Ming Lianxi,Shen Junnan,Pang Weijun
Background Skeletal muscle lipid deposition is a key manifestation of obesity, often accompanied by decreased exercise capacity and muscle atrophy. Skeletal muscle as the largest organ in the body, makes it challenges for designing targeted drug delivery systems. Lipid nanoparticles (LNPs) are widely used as a safe and efficient delivery carrier, there is limited research on LNPs that specifically target skeletal muscle. Results A LNP designed with five specific receptor complements on its surface, which specifically targets skeletal muscle in vivo in mice, without off-target effects on other tissues and organs. MiR-130a, a regulator of PPARG, which is a key factor in skeletal muscle lipid deposition, was encapsulated with LNP (LNP@miR-130a). In high-fat diet (HFD) mice, LNP@miR-130a effectively reduced skeletal muscle lipid deposition, increased exercise activity and enhanced muscle mass. Interestingly, the myokines in skeletal muscle have also changed which may leading to reduce the adipose tissue weight and liver lipid deposition in HFD mice. Conclusions These results indicated LNP@miR-130a is a promising inhibitor of skeletal muscle lipid deposition and may help alleviate obesity. This study provides new insights for obesity treatment and lays foundation for the development of targeted skeletal muscle therapeutics. Graphical
研究领域:
生物医学
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分子生物学
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药剂学
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DOI
PubMed
高影响因子
Neurophotonics
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2020
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IF 2.537
Yusha Li,Jianyi Xu,Jingtan Zhu,Tingting Yu,Dan Zhu
Three-dimensional visualization of the innervation in skeletal muscles is helpful for understanding the morphological structure and function. iDISCO, a whole-mount immunolabeling and clearing technique, provides a valuable tool for volume imaging of intramuscular nerve fibers but suffers from the nonspecific staining caused by the anti-mouse secondary antibody when using the murine primary antibody. We developed a modified iDISCO method by introducing pretreatment of ScaleCUBIC-1 reagent, termed m-iDISCO. The m-iDISCO method could eliminate the nonspecific staining and achieve uniform and complete labeling of nerve fibers in various muscles with mouse anti-neurofilament primary antibody. Combining the m-iDISCO method with light-sheet microscopy enabled us to visualize the innervation of adult mouse tibialis anterior and trace the nerve fibers from extramuscular branches to intramuscular terminal branches. This method represents an effective alternative for studying the innervation of intact skeletal muscles in health and disease.
研究领域:
神经生物学
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肌肉生理学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
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IF 4.7
Shuo Zhang,Shuang Guo,Pengyu Wang,Yan Song,Leiming Yang,Qiyu Sun,Qi Huang,Youzhi Zhang
Background Skeletal muscle atrophy is a clinical concern in diabetic nephropathy, and without effective therapeutic approaches. Massive evidence has demonstrated that dapagliflozin, a sodium-glucose co-transporter 2 inhibitor can relieve diabetic nephropathy by inhibiting glucose re-absorption or podocyte pyroptosis. Nevertheless, whether dapagliflozin could treat skeletal muscle atrophy or the potential protection mechanism in diabetic nephropathy mice is unclear. Methods The variety of approaches were used to assess the particular histology-associated characteristics, mRNA, and protein expression. These included examing the morphology of renal and skeletal muscle tissues through H&E staining, detecting mRNA and protein expression through real-time PCR and Western blot analysis, and monitoring fasting blood glucose levels by using Blood Glucose Monitor Test Kits. Results Dapagliflozin mitigated renal tissue injury with podocyte protein-nephrin and skeletal muscle atrophy effectively with mitochondrial-related proteins. Meanwhile, our research revealed that Casp3 was the target gene and dapagliflozin could decrease the expressions. Subsequently, we verified that dapagliflozin can effectively decrease canonical pyroptosis pathway proteins, which include Gasdermin D, NLRP3, Casp1, and ASC. Meanwhile, Palmitic acid (PA) induced Gasdermin E-N fragment (non-canonical pyroptosis protein) in C2C12 cells, and then released the inflammatory molecules such as IL-1β, IL-18, and NF-kappaB, which were suppressed by dapagliflozin treatment. Aside from that, dapagliflozin demonstrated a good binding affinity to the Casp3 and Gasdermin D protein, whereas it had a less binding affinity with NLRP3, Casp1, ASC, and Gasdermin E. At last, the Gasdermin D inhibitor can reverse the therapeutic effect of dapagliflozin. Conclusion Dapagliflozin alleviates skeletal muscle atrophy in diabetic nephropathy mice, which is through the Gasdermin D-mediated canonical pyroptosis pathway.
研究领域:
医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Foods
·
2023
·Vol. 12
·期 13
·2471
·
IF 5.2
Jinjie Li,Yi Li,Xiangying Suo,Jiangtao Li,Da Huang,Guangning Kou
Bayberry is known to be a rich source of natural flavonoids and has been reported to have various health-promoting abilities. However, its function on regulating skeletal muscle fiber type remains unclear. This study examined whether bayberry extract affects skeletal muscle fiber type by promoting fast myofiber formation, as well as the potential molecular mechanism. After eight weeks, the “Biqi” bayberry extract (BBE) groups mice displayed markedly enhanced grip strength and improved metabolic rate compared to the control group mice. BBE also significantly increased myofibers size, LDH activity, MyHC-IIb (fast-twitch mRNA) expression, and the percentage of fast-twitch myofibers, while decreasing SDH activity, MyHC-I (slow-twitch mRNA) expression, and slow-twitch myofibers percentage in the skeletal muscle of the mice. The effect of BBE on regulating skeletal muscle fiber type remodeling is likely attributed to its activation of the Akt-FoxO1 pathway. Our findings indicated that BBE can effectively regulate the expression and proportion of fast-twitch fibers, making it a potential therapy for improving glucose homeostasis of skeletal muscle.Keywords:bayberry extract;skeletal muscle;fast-twitch fibers;myofiber type;FoxO1
研究领域:
药理学
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分子生物学
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运动生理学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2025
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IF 19
Yeying Lin,Xudan Xing,Xinchang Kang,Mingjie Liu,Tianhua Xiao,Yangengchen Zhong,Chuyang Xiang,Chengyun Ning,Yuhe Jiang,Guoxin Tan,Lei Zhou
Although hydrogel-based therapies have demonstrated promising results in treating volumetric muscle loss (VML), addressing diabetic skeletal muscle defects remains a major challenge due to the interplay of chronic inflammation and impaired regenerative capacity associated with diabetes mellitus. This study presents a novel multifunctional hydrogel bioelectronic conductor designed specifically for diabetic VML repair. The hydrogel, which self-assembles from mannose receptor-binding glucomannan, polydopamine-functionalized conductive polypyrrole, and gelatin, mimics the mechanical properties of native muscle tissue while providing immunomodulatory and electrocoupling effects. Multiple crosslinking mechanisms, involving both dynamic covalent and noncovalent interactions, endow the hydrogel with enhanced tissue adhesion (adhesion strength of 69.41 kPa to soft tissue), elasticity (100% self-recovery), and rapid self-healing ability (less than 1 min). The electrically conductive hydrogel-based elastic bioelectronics can reestablish effective electrical coupling with electroactive muscle tissue, while its intrinsic immunomodulatory properties induce M2-type macrophage polarization to alleviate chronic inflammatory response. In a diabetic rat VML defect model, the hydrogel bioelectronic conductor facilitated effective immunomodulation, muscle regeneration, and functional recovery of injured VML. These results suggest that the integration of tissue-mimicking mechanics with both immunomodulatory and conductive properties offers a promising therapeutic approach for diabetic skeletal muscle repair.
研究领域:
生物医学工程
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再生医学
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材料科学
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产品关联
DOI
高影响因子
Autophagy
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2024
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IF 14.6
Qingyuan Zhang,Chunhui Chen,Ye Ma,Xinyi Yan,Nianhong Lai,Hao Wang,Baogui Gao,Anna Meilin Gu,Qinrui Han,Qingling Zhang,Lei La,Xuegang Sun
Regressing the accelerated degradation of skeletal muscle protein is a significant goal for cancer cachexia management. Here, we show that genetic deletion of Pgam5 ameliorates skeletal muscle atrophy in various tumor-bearing mice. pgam5 ablation represses excessive myoblast mitophagy and effectively suppresses mitochondria meltdown and muscle wastage. Next, we define BNIP3 as a mitophagy receptor constitutively associating with PGAM5. bnip3 deletion restricts body weight loss and enhances the gastrocnemius mass index in the age- and tumor size-matched experiments. The NH2-terminal region of PGAM5 binds to the PEST motif-containing region of BNIP3 to dampen the ubiquitination and degradation of BNIP3 to maintain continuous mitophagy. Finally, we identify S100A9 as a pro-cachectic chemokine via activating AGER/RAGE. AGER deficiency or S100A9 inhibition restrains skeletal muscle loss by weakening the interaction between PGAM5 and BNIP3. In conclusion, the AGER-PGAM5-BNIP3 axis is a novel but common pathway in cancer-associated muscle wasting that can be targetable. Abbreviation: AGER/RAGE: advanced glycation end-product specific receptor; BA1: bafilomycin A1; BNIP3: BCL2 interacting protein 3; BNIP3L: BCL2 interacting protein 3 like; Ckm-Cre: creatinine kinase, muscle-specific Cre; CM: conditioned medium; CON/CTRL: control; CRC: colorectal cancer; FUNDC1: FUN14 domain containing 1; MAP1LC3A/LC3A: microtubule associated protein 1 light chain 3 alpha; PGAM5: PGAM family member 5, mitochondrial serine/threonine protein phosphatase; S100A9: S100 calcium binding protein A9; SQSTM1/p62: sequestosome 1; TOMM20: translocase of outer mitochondrial membrane 20; TIMM23: translocase of inner mitochondrial membrane 23; TSKO: tissue-specific knockout; VDAC1: voltage dependent anion channel 1.
研究领域:
肿瘤学
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细胞生物学
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肌肉生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
·
2018
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IF 3.247
Na Zhang,Yahui zhou,Qingxin Yuan,Yao Gao,Yan Wang,Xingyun Wang,Xianwei Cui,Pengfei Xu,Chenbo Ji,Xirong Guo,Lianghui You,Nan Gu,Yu Zeng
T2DM is a global health problem that seriously lowers the quality of life and insulin resistance makes a considerable contribution to the pathophysiology of T2DM. Long noncoding RNAs (lncRNAs) have emerged as important regulators in glucose and lipid metabolism. However, comprehensive analysis of lncRNAs in db/db mice skeletal muscle and their potential roles involved in skeletal muscle insulin resistance (IR) remains poorly characterized. Here, we identified 331 lncRNAs, 172 upregulated and 159 downregulated (|fold change|>2, q<0.05), differentially expressed in db/db mice skeletal muscle. Gene Ontology analysis, Pathway analysis and Gene Set Enrichment Analysis of network gene expression revealed the potential functions of dysregulated lncRNAs may involve skeletal muscle function, fatty acid metabolism and the PPAR signaling pathway. In addition, differentially expressed lncRNAs were verified in skeletal muscle from the widely known IR mouse models ( db/db and ob/ob mice). Further validation of lncRNAs in C2C12 myotubes exposed with various concentrations of palmitate uncovered that lncRNAs were responsive to palmitate exposure at the high concentrations (0.5mM and 0.75mM). Coexpression analysis revealed the key lncRNA-mRNA interactions and indicated a potential regulatory role of lncRNAs. Moreover, we characterized two candidate lncRNAs Gm15441 and 3110045C21Rik by a comprehensive examination of their genomic context and validated their expression with neighboring genes (Txnip and Ddr2) by the Spearman correlation analysis. Collectively, these findings improve our understanding of lncRNAs that mediate skeletal muscle insulin resistance in diabetes and represent potential molecular therapeutic targets to improve insulin sensitivity and associated metabolic diseases.
研究领域:
分子生物学
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代谢疾病
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遗传学
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产品关联
DOI
PubMed
高影响因子
Antioxidants
·
2023
·Vol. 12
·期 5
·1050
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IF 7
Jordi Vignaud,Céline Loiseau,Josiane Hérault,Claire Mayer,Martine Côme,Isabelle Martin,Lionel Ulmann
In recent years, microalgae have become a source of molecules for a healthy life. Their composition of carbohydrates, peptides, lipids, vitamins and carotenoids makes them a promising new source of antioxidant molecules. Skeletal muscle is a tissue that requires constant remodeling via protein turnover, and its regular functioning consumes energy in the form of adenosine triphosphate (ATP), which is produced by mitochondria. Under conditions of traumatic exercise or muscular diseases, a high production of reactive oxygen species (ROS) at the origin of oxidative stress (OS) will lead to inflammation and muscle atrophy, with life-long consequences. In this review, we describe the potential antioxidant effects of microalgae and their biomolecules on mitochondrial functions and skeletal muscular oxidative stress during exercises or in musculoskeletal diseases, as in sarcopenia, chronic obstructive pulmonary disease (COPD) and Duchenne muscular dystrophy (DMD), through the increase in and regulation of antioxidant pathways and protein synthesis.Keywords:microalgae;antioxidant molecules;redox homeostasis;oxidative stress;mitochondrial function;musculoskeletal diseases;exercise
研究领域:
生物化学
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医学
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营养学
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DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2025
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IF 8.1
Xia Hangbin,Yang Chen,Li Huili,Huang Lingwei,Zeng Zhen,Chi Runrun,Yang Ziwei,Wang Yuzen,Chang Jiang,Jiao Yiren,Li Wenzhong
Muscle satellite cells (MuSCs) play a vital role in skeletal muscle regeneration. However, in intractable muscle diseases such as volumetric muscle loss (VML), the quantity and function of MuSCs are significantly reduced, severely limiting the body's inherent muscle regeneration capability. In this study, we propose a novel strategy to modulate the fate of MuSCs using a combination of bioactive magnesium (Mg) and silicon (Si) ions, sustainably delivered through magnesium silicate (MgSiO3, MS) bioceramic-based scaffolds. In vitro, Mg and Si ions synergistically promote the proliferation and differentiation of MuSCs. Similarly, Mg and Si ions derived from MS/poly (L-lactic acid) (MS/PLLA) composite scaffold also increases the proliferation and differentiation ability of MuSCs. Furthermore, MS/PLLA composite scaffolds facilitate the activation of MuSCs, regeneration of muscle fiber, and neovascularization, while inhibiting fibrosis, thereby effectively restoring muscle function and promoting tibialis anterior muscle functional regeneration in a VML mouse model. Mechanistically, the combination of Mg and Si ions promotes the activation and proliferation of MuSCs by activating the Notch1-Hes1 pathway. Besides, the combination of Mg and Si ions also improves the differentiation of MuSCs by up-regulating Myod and Myog, and enhances fusion by up-regulating Mymk and Mymx expression. The outcomes of our research introduce a promising approach to the treatment of skeletal muscle injuries and related diseases.
研究领域:
再生医学
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生物材料学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2023
·
IF 5.2
Lanting Wei,Xiang Wang,Junjie Fu,Jian Yin,Jing Hu
The current therapy for muscle injury is facing challenges in tissue self-regeneration and function restoration, which declines steeply with age. Tissue engineering is a promising strategy for treating skeletal muscular disorders. Natural polysaccharides have great potential to support cell growth and attachment as tissue-engineered scaffolds. A three-dimensional (3D) porous hydrogel scaffold has been prepared based on the double network of natural polysaccharide sodium alginate (SA), chitosan (CS) and Ca 2+ ions through the freeze-drying process. The physical, mechanical, and biological properties of the CS/SA/Ca 2+ hydrogel scaffold can be controlled by adjusting the SA/CS ratio. The physically cross-linked double network hydrogel showed good biosafety, high stability and satisfactory degradation rate . When the CS/SA molar ratio was 1:1.2 (H-1.2 group), the pore size and compression modulus of the double network hydrogel were 104.06 ± 2.64 µm and 40.00 ± 2.52 kPa, respectively. The results of in vitro evaluation showed that the 3D structure of the CS/SA/Ca 2+ double network hydrogel could well support adhesion and proliferation of C2C12 murine myoblasts and porcine skeletal muscle stem cells. The best cell growth effect was achieved in the H-1.2 group. The physically cross-linked CS/SA/Ca 2+ double network hydrogel can be a promising printable material as the cell scaffold in applications of skeletal muscle tissue engineering.
研究领域:
组织工程
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生物材料
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生物医学工程
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细胞生物学
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产品关联
DOI
高影响因子
FASEB JOURNAL
·
2023
·Vol. 37
·期 4
·e22866
·
IF 4.8
Shan-Yan Gao,Yong-Ping Liu,Ri Wen,Xin-Mei Huang,Ping Li,Yu-Hang Yang,Ni Yang,Tie-Ning Zhang
Uncontrolled diabetes causes a catabolic state with multi-organic complications, of which impairment on skeletal muscle contributes to the damaged mobility. Kcnma1 gene encodes the pore-forming α-subunit of Ca 2+ - and voltage-gated K + channels of large conductance (BK channels), and loss-of-function mutations in Kcnma1 are in regards to impaired myogenesis. Herein, we observed a time-course reduction of Kcnma1 expression in the tibialis anterior muscles of leptin receptor-deficient (db/db) diabetic mice. To investigate the role of Kcnma1 in diabetic muscle atrophy, muscle-specific knockdown of Kcnma1 was achieved by mice receiving intravenous injection of adeno-associated virus-9 (AAV9)-encoding shRNA against Kcnma1 under the muscle creatine kinase (MCK) promoter. Impairment on muscle mass and myogenesis were observed in m/m mice with AAV9-sh Kcnma1 intervention, while this impairment was more obvious in diabetic db/db mice. Simultaneously, damaged mitochondrial dynamics and biogenesis showed much severer in db/db mice with AAV9-sh Kcnma1 intervention. RNA sequencing revealed the large transcriptomic changes resulted by Kcnma1 knockdown, and changes in mitochondrial homeostasis-related genes were validated. Besides, the artificial alteration of Kcnma1 in mouse C2C12 myoblasts was achieved with an adenovirus vector. Consistent results were demonstrated by Kcnma1 knockdown in palmitate-treated cells, whereas opposite results were exhibited by Kcnma1 overexpression. Collectively, we document Kcnma1 as a potential keeper of mitochondrial homeostasis, and the loss of Kcnma1 is a critical event in priming skeletal muscle loss in diabetes.
研究领域:
糖尿病
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肌肉生物学
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分子遗传学
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细胞生理学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）